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Objective: To evaluate the effectiveness of the addition of first-trimester biochemistry to fetal nuchal translucency (NT) measurement in the Combined Test when screening for trisomy 21 in twin pregnancies., Methods: Maternal serum free beta-hCG and PAPP-A were determined at 8 to 12 weeks and fetal NT was measured at 11 to 14 weeks. The individual risks were estimated for each of the fetuses using both NT screening alone and the Combined Test. An invasive diagnostic procedure was offered when the risk was 1:250 or over in either one of the fetuses. In the first period, only the results of NT screening were clinically applied. After previous analysis, the Combined Test was introduced into clinical practice., Results: In the two-and-a-half-year study period, a complete follow-up was obtained in 100 twin pregnancies. Three fetuses (two pregnancies) with trisomy 21 were detected by both methods. The false-positive rate achieved by NT screening (14.3% of pregnancies and 8.6% of fetuses) was substantially reduced when first-trimester biochemistry was added in the Combined Test (5.1% of pregnancies and 3.6% of fetuses)., Conclusion: The Combined Test appears to maintain the detection rate achieved by NT screening for trisomy 21 in twin pregnancies, but false-positive rates and invasive diagnostic procedures are reduced., (Copyright 2005 John Wiley & Sons, Ltd)

We report here a case of twin reversed arterial perfusion sequence with transposition of great arteries in the pump twin. Color Doppler and fetal echocardiographic examination revealed an acardiac, anencephalic twin without upper limbs and a pump twin with transposition of great arteries. To our knowledge despite multiple anomalies reported in the acardiac twin, major anomalies, especially of a cardiac type are extremely rare and not reported in the pump twin, which maintains circulation. Management is directed at saving the pump fetus; therefore, we believe that during sonographic exam, emphasis should be placed on associated organ anomalies or complications that may hamper viability of the pump.

Background: To investigate the association between low birthweight and diabetes in a population-based Swedish twin sample. Method A cohort of 11 162 same-sexed Swedish twins born between 1906 and 1958 was used in order to investigate the risk of developing Type 2 diabetes between and within twin pairs by utilizing random effects linear models., Results: Between pairs there was a significant increase in risk of developing Type 2 diabetes for a 1-kg increase in their mean birthweight (odds ratio [OR] = 2.13; P < 0.01), adjusted for age, sex, body mass index (BMI), and smoking status. The corresponding risk within pair was 2.03 (P = 0.07) for monozygotic twins and 1.15 (P = 0.71) for dizygotic twins. The test of the heterogeneity of the within and between effects showed no significant difference between the estimates., Conclusions: The study suggests that reduced fetal growth increase the risk of Type 2 diabetes due to an in utero programming effect possibly caused by intrauterine malnutrition. However, it does not exclude the possibility of a common genetic mechanism.

Fetus in fetu is an extremely rare condition defined by the presence of both axial skeleton and organoid formations in the parasitic mass. Besides some authors assuming that fetus in fetu and highly-differentiated teratomas are part of the same pathogenic spectrum, it has been emphasized that these criteria indicate a rather different embryogenetic mechanism. We herein report the first case to our knowledge developed in the ventral mediastinum that was thought to be a tumor before birth. The literature is reviewed and we propose a new explanation for the development of this rare anomaly, based on a defective implantation., (Copyright 2004 S. Karger AG, Basel)

Conjoined twins can be classified on the basis of the site of union; thus, three main types can be described: (a) ventral union, (b) dorsal union, and (c) rarer forms of union. Ventral union is characterized by the fusion of the two embryos on the ventral side (eg, the abdomen). Dorsal union twins are joined on the dorsal aspect (eg, the vertebral column or occipital bone). Ventral union twins include the group of crucipage twins (ventral midline structures at 90 degrees to the dorsal midline structures), which show interesting features in the organization of the midline. Twins conjoined at the head and chest are called cephalothoracopagus twins. The cephalothoracopagus variety called "Janus" is characterized by the presence of two opposite faces, which are composite structures half of which belong to one twin and half to the other. A complete set of five variants of cephalothoracopagus is presented and, to the authors' knowledge, analyzed for the first time with multi-detector row helical computed tomography. This modality is an invaluable tool for obtaining high-resolution images of the brain, chest, abdomen, and spine and for demonstrating organ position, shared viscera, and limited vascular anatomy. In addition, data acquired in three-dimensional volumes can further be manipulated and then reconstructed. For this purpose, the authors developed dedicated software for three-dimensional reconstruction to analyze data from specimens preserved in formalin. The anatomic findings are discussed here for their embryologic value and to revise the classification of cephalothoracopagus twins. These data offer detailed information for accurate comprehension of imaging studies and for theoretical studies concerning the formation of several anatomic structures., (Copyright RSNA, 2004)

Prenatal acquisition of leukaemia-associated gene rearrangements is a well-established phenomenon. This is the first report of a complex cytogenetic clone, in association with an ETV6/AML1 fusion, developing in utero. Identical twin girls, aged 4 years, developed ETV6/AML1-positive acute lymphoblastic leukaemia (ALL) within 3 months of one another. Both demonstrated an identical four way, variant t(12;21). There was gain of an AML1 signal in twin 1 and loss of an ETV6 one in twin 2 at interphase. This unique case study demonstrates that ETV6/AML1 fusion and the associated complex chromosomal rearrangements occurred in utero. Clonal expansion of the abnormal cell in one twin was followed by metastasis to the other. There was a prolonged preleukaemic phase, which lasted well into childhood. The short time between the two diagnoses of ALL suggests a common precipitating event. The significance of the different secondary markers remains unclear., (Copyright 2004 Blackwell Publishing Ltd)

Twinning has fascinated human beings over the centuries. New technologies and large study groups have led to improved documentation of frequency and complications in twin pregnancies and long-term outcomes. Artificial reproductive technologies have led to a pronounced rise in numbers of dizygotic and monozygotic twins. Although spontaneous dizygotic twinning is clearly associated with increased concentration of follicle-stimulating hormone and ovulation of more than one egg, causes of monozygotic twinning remain illusive. Twin studies are used increasingly to study complex traits and disorders: however, caution is suggested, since twins might not be representative of a typical singleton pregnancy. Monozygotic twinning seems to represent an anomaly in itself, with an increased number of spontaneous abortions and structural congenital anomalies. Both monozygotic and dizygotic twins have growth rates that slow at 30 weeks in utero and might be programmed both developmentally and biochemically earlier in pregnancy to have different responses at birth and after birth compared with singletons.

Previous studies on concordant acute lymphoblastic leukemia (ALL) in identical twins have identified the leukemia as monoclonal with MLL or ETV6-RUNX1 gene fusion as early or initiating events in utero. In the latter case, postnatal latency is associated with secondary genetic events such as ETV6 deletion. We describe here a pair of infant twins with concordant acute monoblastic leukemia (AML). They are a unique pair in that their leukemia blasts display extensive intraclonal chromosomal diversity. Comparison of the leukemic cells between the two twins by karyotype and fluorescence in situ hybridization identifies a common or shared stem line and extensive subclonal diversity for which the twins' leukemic populations are divergent. This case of leukemia illustrates in utero initiation with early imposition of chromosomal instability, the progressively divergent evolution of which can be mapped in the twins into pre- and postnatal periods., (Copyright 2003 Wiley-Liss, Inc.)

Sonography has made a dramatic impact on the obstetric management of complicated twin pregnancies. This is based in part on the ability to use prenatal US to diagnose syndromes and complications of MC twinning. All twin pregnancies are at high risk for perinatal morbidity and mortality compared with singleton gestations, but when one of the described complications is recognized, the difficulties in management are compounded dramatically. Despite the relative rarity of some of the entities described, it is vitally important to be familiar with these problems and their sonographic evaluation and diagnosis.

Objectives: Twin studies present a unique opportunity to examine the association of birth weight with adult life phenotypes in a design that naturally accounts for maternal factors and a range of early environmental factors, which might potentially bias the association. In this study, we explored the association of birth weight with osteoporosis (OP) and osteoarthritis (OA), in a large national cohort of female twins., Methods: Intra-pair differences between the reported birth weight of the twins (n=4008) were examined for an association with: (i) intra-pair differences in bone mineral density (BMD) and bone mineral content (BMC) at the lumbar spine, hip and forearm using linear regression; and (ii) osteoarthritis status in pairs discordant for radiographic disease at the hand, hip and knee using matched logistic regression. The confounding influences of height and weight were taken into account., Results: The mean age of the twins was 47.5+/-12.3 yr. Intra-pair differences in birth weight were significantly associated with BMD at the spine (P=0.047), total hip (P=0.016) and femoral neck (P<0.001), but not at the forearm (P=0.245). These were entirely explained by the birth weight association with height and weight. The associations of intra-pair differences in birth weight and BMC were highly significant (P<0.001) at all sites, but were partly explained by adjustment for adult height and weight. We found no clear association between intra-pair birth weight differences and OA in twins discordant for any of the radiographic OA phenotypes at any site., Conclusions: Bone mass and especially BMC are highly associated with birth weight. These associations are accounted for mainly by environmental factors that are independent of maternal factors such as gestational age, maternal smoking and nutrition, and are largely mediated by skeletal size and particularly adult height. Birth weight does not appear to be a major influence on the later development of radiographic OA in women.

Purpose of Review: Monochorionic compared with dichorionic twins have disproportionately high fetal loss rates, perinatal mortality and morbidity. This is because of the unpredictable vascular anastomoses and the often asymmetrical distribution of the single placenta between both twins., Recent Findings: The pathophysiology of twin-to-twin transfusion syndrome is usually explained on an angioarchitectural basis, although certain hemodynamic and hormonal factors also may be involved. The results of the large randomized trials on amnioreduction, fetoscopic laser coagulation and septostomy are still awaited. An update is given on hardware and instruments required for fetoscopic laser. Subsequently, the problem of the monochorionic twin set with severe early discordant growth is addressed. Several etiological mechanisms have been proposed, but little is known of its natural history. Also, umbilical artery Doppler waveforms may not have the same predictive value as in singletons. Prophylactic laser coagulation of the vascular anastomoses to protect against the adverse effects of single intrauterine demise, has so far not been shown to confer any benefit in outcome. Finally, pathophysiology and management of discordant structural and chromosomal anomalies in monochorionic twins are discussed. Laser and monopolar coagulation, which can be introduced through a needle, may be used for selective feticide in early pregnancy or low hemodynamic conditions. Bipolar coagulation seems more effective at later gestational ages and normal hemodynamic conditions., Summary: Our insight into the complications associated with monochorionic twins has increased in recent years. It is hoped that this will lead to better surveillance and ultimately an improved outcome for these high-risk pregnancies.

Objective: The purpose of this study was to determine the effect of birth weight discordance (BWD) and prematurity on twin neonatal outcome by measuring Apgar scores and blood glucose concentrations at birth., Methods: This was a retrospective cross-sectional study. All twins born at NY Methodist Hospital between January 1998 and December 2001 were eligible. Excluded were fetal deaths, maternal systemic disease, maternal infections, major neonatal malformations, neonates with birth weight < 500 g and multiple gestation greater than 2. BWD was defined as intrapair difference in birth weight expressed as percentage of the larger twin greater than 20% and prematurity as gestation of less than 37 weeks. Hypoglycemia was defined as blood glucose concentration < 40 mg/dl., Results: There were 75 (48%) preterm and 80 (52%) term twin pairs. Nineteen (12%) of the preterm and 15 (9.6%) of the term showed BWD. Mean Apgar scores at 1 and 5 minutes were higher for the term twins as expected. Neither prematurity nor hypoglycemia was present predominantly in BWD twins. Twelve of the preterm and six of the term BWD twins showed evidence of hypoglycemia., Conclusion: Hypoglycemia in the early hours of postnatal life is relatively common in preterm BWD twins. Blood glucose measurement using reagent strips is an efficient way of monitoring blood glucose concentrations in these infants.

We describe a monochorionic, diamniotic twin with renal agenesis who received amniotic fluid from his normal co-twin by spontaneous rupture of the amniotic septum between them. By 16 weeks of gestation the presence of severe oligohydramnios in one twin had resulted in renal agenesis, but not in the other twin, who did not have oligohydramnios. By 20 weeks of gestation, the two amniotic fluid volumes had become the same in both twins. At 33 weeks, the twins were delivered by cesarean section. Despite intensive respiratory care, the twin with renal agenesis died from severe pneumomediastinum on day 3. At autopsy, pulmonary hypoplasia was demonstrated in that twin. This experiment of nature demonstrates that oligohydramnios during the early canalicular stage of pulmonary development (gestational age, 16-20 weeks) may be pathogenically important in pulmonary hypoplasia., (Copyright 2002 Wiley-Liss, Inc.)

Aim: To determine the neurodevelopmental morbidity in the surviving twin after fetal or infant death of the co-twin., Methods: Twin pregnancies with an antepartum or infant death delivered between 1981 and 1992 were identified from the Northern Perinatal Mortality Survey. Information on the neurodevelopmental morbidity of infant survivors of a deceased co-twin was obtained by a questionnaire sent to the community paediatrician or general practitioner., Results: A total of 111 children who survived infancy after the fetal death of the co-twin (group 1) and 142 from liveborn twin pairs in which one twin died in infancy (group 2) were traced. Responses were received from 97 (87%) and 130 (92%) respectively. In group 1, the cerebral palsy prevalence was 93 (95% confidence interval (CI) 43 to 169) per 1000 infant survivors; it was more common in like-sex pairs (8/70) with a prevalence of 114 (95% CI 51 to 213) compared with 45 (95% CI 1 to 228) per 1000 infant survivors in unlike-sex pairs (1/22). The overall prevalence of neurodevelopmental morbidity (including developmental delay) was 175 (95% CI 106 to 266) per 1000. In group 2, the cerebral palsy prevalence was 154 (95% CI 84 to 223) per 1000 infant survivors in like-sex (16/104) and 77 (95% CI 9 to 251) in unlike-sex (2/26) survivors; the overall prevalence of neurodevelopmental morbidity was 246 (95% CI 172 to 320) per 1000., Conclusions: The risk of cerebral palsy is increased in the surviving twin after a fetal or infant co-twin death compared with the general twin population. Like-sex twins are at greater risk than unlike-sex. The probable cause, in addition to the consequences of prematurity, is twin-twin transfusion problems associated with monochorionicity.

We describe, to our knowledge, the first case of a pulmonary malformation called acinar dysplasia occurring at a surviving fetus after selective embryo reduction in a bichorionic pregnancy. The chronological and histological observations suggest that this anomaly may be linked with a feticide achieved at 13 week's gestation. Literature review concerning selective embryo reduction shows rare cases of vascular connections in bichorionic pregnancies especially during the first half of gestation, that can explain in part the apparition of survivor's anomalies.

We report a rare case of covered cloacal exstrophy variant with a hemiphallus trapped within partially closed bladder halves. The persistence of the cloacal membrane until at least 18 weeks' gestation, confirmed by antenatal ultrasound scanning, is discordant with existing theories of embryogenesis of cloacal exstrophy. The clinical presentation highlights the need for careful assessment, before and during surgery, to obtain a complete understanding of the anatomic defect before gender assignment and appropriate reconstructive efforts. A multispecialty approach and antenatal counseling are important, especially when only one fetus of twins has major birth defects.

Monozygotic twins with chromosome 22q11 microdeletions offer an ideal situation to observe the association of microdeletion and disrupted cardiovascular patterning. We report monozygotic twins concordant for 22q11.2 microdeletion but discordant for cardiovascular patterning. Both twins showed identical intracardiac defects including tetralogy of Fallot with pulmonary atresia. Nevertheless, their great vessel patternings were variable. These twins show that the mispatterning of the great vessels may not correlate with intracardiac morphogenesis. The discordant development of the great vessels, especially in the pulmonary vascular system, has clinical significance for prognosis. The phenotypic variability of cardiovascular anomalies seen in 22q11 microdeletion cannot be explained on the basis of genotypic difference.

Twin gestations are at significant increased risk for adverse perinatal outcome. As a result, although prospective randomized data is lacking, increased fetal surveillance has been advocated for twins. Growth concordance is considered a reassuring sign in twins and conversely, discordancy to possibly reflect a hostile intrauterine environment at least to the smaller twin. Consequently, increased surveillance of discordant twins is commonly practiced. Monochorionic twins are at further risk for type-specific perinatal complications, for example, twin-twin transfusion syndrome. Recently, precise first-trimester depiction of chorionicity has enabled early antepartum stratification of twin gestations according to chorionicity, in comparison with previous later (mid- and third-trimester) ultrasonographic diagnosis of chorionicity. This immediately leads to the question whether antenatal testing of twins should differ according to chorionicity? Review of the literature supports that despite the existence of complications unique to monochorionic twin gestations, dichorionic twins sustain an increased risk of adverse perinatal outcome (such as fetal growth restriction) in comparison with singletons, and that close antenatal fetal surveillance of twins should be performed, irrespective of chorionicity.

Objective: To tabulate genetic results and obstetric outcomes of twin pregnancies after first-trimester chorionic villus sampling (CVS)., Methods: The study included 262 consecutive women with twin pregnancies who had first-trimester CVS between 1988 and 1998., Results: Major indications for prenatal diagnosis included maternal age (n = 82), pregnancies after intracytoplasmic sperm injection (n = 114), or both (n = 33). Among 524 fetuses, 519 were sampled adequately. Cytogenetic results were incorrect because of sampling the same fetus twice in two pregnancies. In three pregnancies, contamination caused by mixed sampling made cytogenetic results uncertain. Correct genetic diagnoses were obtained in 509 fetuses, 24 of which had chromosomal abnormalities on direct preparations and four of which had monogenetic conditions. Additional invasive procedures were done on five occasions. Fifteen fetuses were terminated selectively. The total fetal loss rate was 5.5% (28 of 509). The indication for the procedure did not significantly determine the fetal loss rate. The mean +/- standard deviation (SD) gestational age at birth was 35.9 +/- 2.9 weeks, and the mean +/- SD birth weights for twins A and B were 2429 +/- 589.1 g and 2378 +/- 588.5 g, respectively., Conclusion: First-trimester CVS is an accurate means of prenatal genetic diagnosis in twins, offering early selective termination in cases of abnormal genetic results in one of the fetuses.

A case of twin pregnancy with intrauterine death of one foetus during the 19th week of pregnancy has been described and the obstetric approach is reported. Pregnancy was actively continued with the following procedure: 1. Tocolysis, 2. Anti-infective prophylaxis; 3. Monitoring of coagulation on factor; 4. Weekly echotomography. In the 39th week the baby was delivered by caesarean section. The baby was discharged in good health on the 5th day after delivery.

A review of over 1,800 publications concerning the embryology and pathologic anatomy of conjoined twins provides convincing evidence that they all result from the secondary union of two originally separate monovular embryonic discs. This "fusion" theory seems to be confirmed by the adjustments to union and the pattern and incidence of specific anomalies at the proposed sites of conjunction in more than 1,200 cases, all of which can be arranged in two uninterrupted series of cases, the one united dorsally (in the neural tube) and the other, ventrally (over a shared a yolk sac). No theoretical "fission" of the vertebrate embryo at any stage of development, in any plane, in any direction can explain (1) the selection of the observed sites of fusion, (2) the details of the union, or (3) the limitation to the specific areas in which the twins are found to be joined. Part I of this disquisition deals with the pertinent normal and theoretical embryology, the adjustments to union, and the parasitic cases, as well as conjoined triplets and quadruplets, and a comparison of oviparous and viviparous embryos. Part II (in a subsequent issue of this journal) will compare and correlate the abnormalities of the various organ systems involved in 1,200 cases., (Copyright 2000 Wiley-Liss, Inc.)

A complex chromosome rearrangement (CCR) with eight breakpoints resulting in four derivative chromosomes (4, 11, 12 and 13) was detected prenatally in a male fetus of a twin pregnancy. The karyotype of the female second fetus was normal. The apparently balanced de novo CCR was identified by classical cytogenetic methods and fluorescence in situ hybridization (FISH). We compared these findings with results from spectral karyotyping (SKY)., (Copyright 1999 John Wiley & Sons, Ltd.)

In order to study the pathogenesis of prenatal deformities, we reviewed maternal histories, delivery records, pathology reports, radiographs, and photographs of 90 fetuses with prenatally documented oligohydramnios at gestational ages from 14 weeks to term. The causes of oligohydramnios included premature rupture of membranes (44 cases), fetal renal insufficiency (25 cases), idiopathic (15 cases), and twin-twin transfusion (6 cases). The fetuses were grouped according to gestational age at delivery and duration of oligohydramnios. Sixty-three fetuses (70%) had documented contractures. As expected, contractures were more frequent with earlier onset and longer duration of oligohydramnios. During the 2nd trimester, the frequency of contractures in fetuses with oligohydramnios was 77% compared to 52% in the 3rd trimester (chi(2) = 5.33, 1 df, P =.02). Considering all gestational ages together, 57% of fetuses had contractures after less than 2 weeks of oligohydramnios compared to 81% of fetuses with a longer duration of oligohydramnios (chi2 = 6.23, 1 df, P <.02). The type of contracture varied with gestational age. Clubfoot was the most frequent at all ages, but hand contractures such as camptodactyly were common only in the 2nd trimester while the broad flat hand originally described in Potter sequence was found almost exclusively in the fetuses with oligohydramnios in the 3rd trimester. Of the 63 fetuses with oligohydramnios and contractures, 25 (40%) had either additional malformations or family history that could explain contractures independent of oligohydramnios., (Copyright 1999 Wiley-Liss, Inc.)

Purpose: To establish the appearance of normal fetal cortical development in utero and compare it with the appearance of abnormal cortical development., Materials and Methods: Magnetic resonance (MR) images of the brain in 53 normal and 40 abnormal fetuses at 14-38 weeks gestational age (GA) were reviewed. The GAs at the time of MR imaging visualization of the fissures or sulci were compared with the GA guidelines based on neuroanatomic studies., Results: In normal fetuses, the sulcation landmarks appeared on MR images in the order predicted by using anatomic studies, with a 0-8-week lag in the MR imaging visualization of the sulci compared with the reported time of visualization of the sulci in anatomic specimens. When landmarks were grouped by range of GAs, the expected MR imaging sulcation landmarks in the group with younger GAs than the actual GA were seen in 50 of 53 (94%) normal fetuses, in five of nine fetuses (56%, P < .05) with isolated mild ventriculomegaly, and in 24 of 31 fetuses (77%, P < .05) with other CNS anomalies., Conclusion: Normal fetal cortical maturation at MR imaging follows a predictable course that is slightly delayed compared with that described in neuroanatomic specimens. This maturation is often further delayed in fetuses with CNS abnormalities.

Sonographic examination is essential in the diagnosis and management of twin gestation. It assists in determining the zygosity, assessing fetal anomalies, and is integral to amniocentesis if it is necessary, determining the growth and ruling out discordance, and in intrapartum management. The management of uncommon complications with twins also requires ultrasonic survey. Considering that the incidence of multiple gestation is increasing, it would be prudent to become familiar with the use and benefit of ultrasound with twins.

Objective: The aim of this study was to show the diagnostic possibilities of ultrasound in twin-to-twin transfusion syndrome (TTTS), to demonstrate its usefulness in cases of hemoglobin difference < 5 g/dL in neonates as well as in cases complicated by intrauterine death of one or both twins., Study Design: The study included 4 pairs of twins. In two cases 3 fetuses died in utero. In the other two the hemoglobin difference in newborn infants was < 5 g/dL. The ultrasound examination, evaluating the fetal anatomy and biometry, amniotic fluid volume, placentation, was performed. The special attention was paid to polyhydramnios/oligohydramnios, discordant fetal growth (fetal weight, abdominal circumference), the presence of fetal hydrops, ascites, pericardial effusion. Doppler blood flow velocimetry has been done in umbilical vessels, middle cerebral artery. The data was compared with normal reference values for singleton pregnancies. The waveforms from both uterine arteries were also evaluated to exclude placental insufficiency. Additionally the blood flow through the AV valves was measured to exclude or confirm its regurgitation. Postnatally the hemoglobin difference was evaluated if available and compared with sonographic findings., Results: In all cases inter-twin difference in abdominal circumference was greater than 18 mm and inter-twin weight difference of more than 15%. We observed polyhydramnios/oligohydramnios in all twin pregnancies. It has been found decreased PI in middle cerebral artery in larger fetus (recipient) in all our cases (comparing to single pregnancy). PI values for this vessel in smaller fetuses were within normal range (for single pregnancy). PI values in umbilical arteries of recipients were abnormal (increased PI or absent end-diastolic flow)., Comments: The sonographic criteria seem to be very useful in diagnosis of twin-to-twin transfusion syndrome, especially in cases where the measurement of hemoglobin level is impossible. Doppler blood flow velocimetry in fetal vessels helps to explain the changes in fetal hemodynamics in TTTS.

The effectiveness of variable number tandem repeats (VNTRs) was evaluated in the detection of maternal cell contamination. Nonradioactive PCRs were performed on 30 sets of prenatal tissue using VNTRs as primers. The combination of two VNTRs (YNZ22 and APOB) provided information on all 30 cases, distinguishing maternal-fetal genotype patterns and detecting maternal cell contamination in 5 of 30 prenatal cases. The amplification of these two VNTRs does not require radioactive or fluorescence labeling, and a small gel electrophoresis is sufficient to see the maternal-fetal genotype pattern. By this method, detection of maternal cell contamination in prenatal tissues can be obtained in 1 day, without the use of expensive instruments, thus providing DNA laboratories a very sensitive, rapid, and simple proof pretest on all prenatal tissues before performing the final genetic diagnostic testing.

A policy of expectant management until 32 weeks of gestation in 29 dichorionic pregnancies discordant for growth retardation resulted in an overall mortality of 24% (95% CI 13.9-37.2%) and a handicap of 2.2% (95% CI 0-12.0%). None of the normally grown co-twins died or was handicapped as a result of iatrogenic prematurity.

During donor evaluation for allogeneic bone marrow transplantation (BMT) of a 28-month-old child with juvenile chronic myelogeneous leukemia (JCML) with 46,XY,-7,+mar karyotype, the potential donor twin brother was found to be thrombocytopenic. Subsequent genotype analysis determined monozygosity with 98% probability. Bone marrow analysis of the twin brother revealed the same 46,XY,-7,+mar karyotype and a diagnosis of JCML was made. Metaphase FISH studies documented that mar chromosome in both twins contains the pericentromeric region of chromosome 7 and thus both twins had a partial monosomy of chromosome 7. A possible embryonic origin of del(7) is proposed.

Objective: To test the hypothesis that the (case) twin later to succumb in utero has biparietal diameter measurements (by ultrasound) different from those (control) twins surviving the perinatal period., Material and Methods: Information from the Medical Birth Registry, National Board of Health and Welfare, Stockholm, was used to identify all births in a defined population in southern Sweden with about 20,000 deliveries each year. In 3,019 twin pregnancies between 1973 and 1989, one or both twins were stillborn in 47 cases (gestational duration > or = 28 weeks, birthweight > or = 500 g). For each case pregnancy, two control pregnancies were selected, the matching criteria being: same delivery unit, same parity (0, I, II, III+), similar year of delivery (+/- 1 year) and maternal age (+/- 5 years). Data on ultrasound examinations were extracted from the original medical records. Screening in early second trimester started at one of the units as early as 1973 and at the latest of 12 units in 1982., Results: There was no obvious difference between cases and controls in intra-pair discordant biparietal diameter (BPD) measured in early second trimester. Nor was there any evident difference in the rate of deviant BPD between cases and controls. In all, 8% of dead male and 24% of dead female fetuses were by definition small-for-gestational age (< -2 standard deviations)., Conclusions: No significant difference was seen between cases and controls regarding deviating biparietal diameters. Abdominal diameter may be a better predictor of subsequent fetal death (not analysed in this study), though only about 15% of all dead twins were deemed small-for-gestational age.

A case of monozygotic twins in a 19-year-old primigravida is presented. Ultrasound examination at 15 weeks' gestation showed one twin to have a cystic hygroma and hydrops fetalis. The other twin appeared normal. The twins appeared to occupy the same amniotic cavity. Fluid was taken from the cystic hygroma under ultrasound guidance for karyotyping and this showed 45,XO chromosomes. Conservative management was adopted. Serial ultrasound examination showed deteriorating hydrops and at 26 weeks the first twin died. Intensive monitoring of the remaining twin was undertaken with weekly ultrasound, cardiotocography (CTG), and clotting screens. At 29 weeks' gestation the CTG and clotting were normal, but ultrasound revealed that multicystic encephalomalacia had developed in the second twin. A very thin dividing membrane was seen for the first time between the twins. The parents decided to terminate the pregnancy. Prior to an intracardiac potassium chloride injection, a fetal blood sample was taken which revealed 46,XX chromosomes and a normal clotting screen including natural anticoagulant levels. Labour was then induced. Delivery took place 5 h later and the woman made an uneventful recovery. The mechanism for genetic differences between monozygotic twins is discussed and the literature reviewed. A non-disjunction event around the time of splitting of the twins is proposed as the cause. The prognosis for the remaining twin is also discussed, as is the pathogenesis of the cerebral damage.

Familial Dysautonomia (FD) is an autosomal recessive sensory neuropathy that affects about 1 in 3,700 individuals of Ashkenazi Jewish ancestry. The underlying biochemical and genetic defects are unknown, thereby precluding prenatal diagnosis in at-risk families. Recently, the FD gene (DYS) was mapped with strong linkage disequilibrium to polymorphic markers in the chromosome 9 region q31-q33. In this report, the use of these markers for the prenatal diagnosis of FD by linkage analysis in families with a previously affected child was evaluated. Genomic DNA from appropriate family members was analyzed to construct haplotypes using informative CA repeat polymorphisms closely linked to and flanking the FD locus. The calculation of risk for the prenatal diagnoses was performed by linkage analysis. All seven FD families were informative for the closely linked polymorphic markers and fetal diagnoses were made in eight pregnancies. Six fetal diagnoses were predicted with > 98% accuracy, while two with recombinations were predicted with at least 88% and 92% accuracy. Use of these closely linked markers permitted the reliable prenatal diagnosis of FD in families with a previously affected child.

The purpose of this study was to evaluate the accuracy of antenatal ultrasonography in the detection of fetal anomalies among twin gestations cared for in a specialized antepartum twin clinic. A retrospective study was performed of 245 consecutive twin gestations followed in our twin clinic. The sensitivity, specificity and diagnostic indices of ultrasound to detect prenatal anomalies in the 490 infants delivered from July 1988 to October 1994 were determined. Fourteen infants had isolated congenital anomalies, and ten had multiple anomalies. The overall prevalence of congenital anomalies was 4.9%. Antepartum ultrasound examination had a sensitivity of 88% and a specificity of 100% for the detection of an anomalous infant, with a positive predictive value of 100% and a negative predictive value of 99%. The sensitivity of ultrasound for each individual anomaly within the cohort was 82%, with 100% specificity, 100% positive predictive value, and 98% negative predictive value. Our conclusions are that serial antepartum ultrasound examination of twins for congenital anomalies in our institution is very specific, with high positive and negative predictive values. The sensitivity, while also excellent, has limitations, which should be discussed with the patient.

An acardiac twin in a multiple pregnancy initially develops normally and is a specific complication of monozygous multiple pregnancies. Development results from arterio-arterial and veno-venous anastomoses leading to predominance of one of the twins. The haemodynamic abnormalities in the dominated twin lead to the disappearance of the heart and major morphologic malformations. Outcome is generally unfavourable in 50% of the pregnancies with an acardiac twin. Complications in the healthy twin include heart failure, then hydramnios, and finally premature delivery which is the cause of most of the deaths. Proposed treatment currently relies on treating the heart failure in the healthy twin or interrupting vascularization between the two twins leading to in utero death of the acardiac twin. Antenatal diagnosis is made by echography and is useful for evaluating the prognosis for the pregnancy according to the growth of the acardiac twin.

Fetus-in-fetu is a rare condition presenting as a calcified intra-abdominal mass in the newborn infant. Over 50 cases of fetus-in-fetu have been reported since 1800. Karyotype analysis in 8 cases and protein polymorphisms in 4 documented identical findings in the host and fetiform mass. We report a case of fetus-in-fetu in a newborn female including cytogenetic and molecular studies of both the host and mass. Genotypic information from 7 polymerase chain reaction (PCR) assays representing 4 chromosomes demonstrates heterozygous and identical alleles in the infant and fetus-in-fetu at all loci studied. A review of the literature is provided including a discussion regarding the impact of molecular data on present hypotheses of fetus-in-fetu pathogenesis.

An excess of structural defects occurs in monozygotic twins compared to dizygotic twins or singletons. Among these defects the acardius acephalus or chorangiopagus parasiticus is one of the most rare and severe and a possible cause of pathology to the other twin. Ovulation induction by clomiphene causes an increased frequency of multiple gestation and possibly of monozygotic multiple pregnancy. In the present report, we describe a prenatally diagnosed and autopsied case of acardius acephalus from a pregnancy established after ovulation induction by clomiphene. Approximately 1.4% of pregnancies are accomplished after use of ovulation inducing medication in the Netherlands. A possible etiological role of clomiphene justifies close monitoring of future cases.

Objective: Since the second prenatal trimester is the critical period of massive neural cell migration to the cortex, and fingertip dermal cells migrate to form ridges during this same period, the authors sought to determine whether there are differences in fingertip ridge count in pairs of monozygotic twins discordant for schizophrenia, possibly indicating that a prenatal anatomical insult affected the twins differently., Method: The fingertip dermal ridges of 30 pairs of monozygotic twins (23 pairs in which the twins were discordant for schizophrenia and seven pairs in which both twins were normal) were counted by two persons trained in anthropometric research. Intrapair differences in the counts were then measured, and the differences among the pairs of normal twins were compared with the differences among the pairs discordant for schizophrenia., Results: The twins discordant for schizophrenia had significantly greater absolute intrapair differences in total finger ridge count and significantly greater percent intrapair differences than the normal twins; i.e., their fingerprints were significantly less "twin-like.", Conclusions: The study suggests that various second-trimester prenatal disturbances in the epigenesis of one twin in a pair discordant for schizophrenia may be related to the fact that only one of the twins expresses his or her genetic predisposition toward schizophrenia. This is consistent with a "two-strike" etiology of schizophrenia: a genetic diathesis plus a second-trimester environmental stressor.